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Effects of Cytosine Arabinoside, Daunomycin, Mithramycin, Azacytidine, Adriamycin, and Camptothecin on Mammalian Cell Cycle Traverse¹

Biomedical Research Group, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico 87544

Six chemotherapeutic agents were tested for effects on mammalian cell cycle traverse in synchronized cultures of Chinese hamster cells. Cytosine arabinoside was found to inhibit DNA synthesis, as well as to reduce grossly the rate of progression from G₁ into S. At low dosage levels, daunomycin and adriamycin had only a slight effect upon entry of cells into S, but they were almost totally effective in preventing cells from reaching mitosis, and 5-azacytidine greatly inhibited progression into S phase. However, cells already in S at the time azacytidine was added continued to synthesize DNA but were unable to progress to mitosis. Entry into S was hardly affected by mithramycin, while completion of G₂ was partially inhibited, although the sensitivity of G₂ processes was much less pronounced in mithramycin-treated cells than in cells treated with daunomycin or adriamycin. Camptothecin allowed initiation of DNA synthesis, but it effectively prevented cells from progressing to mitosis in the incubation period allotted in the test protocol.

¹ This study was supported by Contract NIH-CR-(71)-56 from Chemotherapy, National Cancer Institute, NIH, under interagency agreement with the United States Atomic Energy Commission.

Received 5/23/72. Accepted 9/ 5/72.

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